Zhang Wei-Ping, Wei Er-Qing, Mei Ru-Huan, Zhu Chao-Yang, Zhao Meng-Hui
Laboratory of Neurobiology, Zhejiang University Medical School, Hangzhou 310031, China.
Acta Pharmacol Sin. 2002 Oct;23(10):871-7.
To determine whether ONO-1078 (pranlukast), a potent leukotriene receptor antagonist, has neuroprotective effect on focal cerebral ischemia in the rat.
Focal cerebral ischemia was induced by 30 min of middle cerebral artery (MCA) occlusion and followed by 24 h reperfusion. ONO-1078 (0.003-1.0 mg/kg) or vehicle (saline 1 mL/kg) was ip injected 30 min before MCA occlusion and 2 h after reperfusion. The neurological score, infarct volume, neuron density (in cortex, hippocampus, and striatum), brain edema, and albumin exudation around the vessels were determined 24 h after reperfusion.
ONO-1078 slightly improved the neurological deficiency, and dramatically decreased infarct volume and neuron loss which showed a bell shaped dose response effect with highest effect at doses of 0.01-0.3 mg/kg. Enlargement of the ischemic hemisphere and albumin exudation were inhibited at doses of 0.01-1.0 mg/kg.
ONO-1078 has the protective effect on focal cerebral ischemia in rats, which is partially attributed to the inhibition of brain edema. This may represent a novel approach to the treatment of acute cerebral ischemia with cysteinyl leukotriene receptor antagonists.
确定强效白三烯受体拮抗剂ONO-1078（普仑司特）对大鼠局灶性脑缺血是否具有神经保护作用。
通过大脑中动脉（MCA）闭塞30分钟，然后再灌注24小时诱导局灶性脑缺血。在MCA闭塞前30分钟和再灌注后2小时腹腔注射ONO-1078（0.003 - 1.0毫克/千克）或溶剂（生理盐水1毫升/千克）。再灌注24小时后测定神经功能评分、梗死体积、神经元密度（在皮质、海马和纹状体中）、脑水肿以及血管周围白蛋白渗出情况。
ONO-1078轻微改善神经功能缺损，并显著降低梗死体积和神经元丢失，呈现钟形剂量反应效应，在0.01 - 0.3毫克/千克剂量时效果最佳。在0.01 - 1.0毫克/千克剂量下，缺血半球扩大和白蛋白渗出受到抑制。
ONO-1078对大鼠局灶性脑缺血具有保护作用，部分归因于对脑水肿的抑制。这可能代表了一种用半胱氨酰白三烯受体拮抗剂治疗急性脑缺血病的新方法。
